Zirconia catalysts can selectively convert ethanol to propylene and exhibit excellent catalytic stability. However, the effects of crystalline phase of ZrO2 on the catalyst active sites and catalytic performance have not been fully recognized. In this work, when Y or La was doped into ZrO2, the monoclinic to tetragonal phase transition occurred, and the propylene yields were improved to 44.0% and 42.3%, respectively. The effects of different crystalline phases of ZrO2 on the ethanol to propylene reaction were analyzed by density functional theory. Comparing the monoclinic, tetragonal and cubic phases of ZrO2, the tetragonal phase ZrO2 has the lowest oxygen vacancy formation energy and is likely to form oxygen vacancies to convert ethanol to propylene. Moreover, the adsorption energy of ethanol on tetragonal ZrO2 is moderate, which is not only beneficial to ethanol conversion, but also reduces catalyst deactivation caused by excessive adsorption. Therefore, tetragonal ZrO2 shows practical significance for catalyzing ethanol to propylene.